The synchronous electrical discharges in the brain that occur during epilepsy can be mimicked very effectively in brain slices from the rat piriform cortex. The study of epileptogenic "hot spots" deep within this brain region holds great promise in revealing the cellular processes and circuitry responsible for epilepsy. This application proposes the use of voltage imaging and single-cell patch clamp recording to study epileptiform activity in piriform cortex. Voltage imaging produces a detailed picture of the time course of epileptiform activity over a substantial area. This allows us to follow the highly characteristic pattern of development of an epileptiform discharge, which is forecast by weak activity in one site, is initiated in another site, and then propagates through a slice along a specific trajectory. With the ability to use imaging techniques to visualize each of these phases in an epileptiform event, patch electrodes can be positioned to record from single cells in targeted regions and thereby obtain precise information about what individual neurons are doing as an epileptiform event progresses. Using voltage imaging and patch clamp techniques in combination we will test a number of hypotheses regarding the generation of epileptiform discharges, including the role of excitatory synaptic activity, the role of specific excitatory connections, the role of electrical activity in specific sites, the contributions of specific types of neurons, and the role of intracellular calcium. We will make parallel studies of interictal-like and ictal-like activity to weigh the relative contributions of cellular processes and circuitry to different kinds of epileptiform activity. These experiments will thus reveal basic mechanisms responsible for epileptiform activity and thus provide a better conceptual framework for investigating human epilepsy, and for developing pharmacological treatments.